In this randomized study, the effects of 24-week treatment with the GLP-1 analogue liraglutide (1.8 mg subcutaneous injection once a day) versus placebo on LV function in 241 stable chronic HF patients with reduced LVEF with and without type 2 diabetes mellitus (T2DM) was investigated.

Main results

The mean absolute increase in LVEF was 0.7±5.4% in the liraglutide group and 1.5±5.0% in the placebo group (mean difference −0.8%, 95% CI: −2.1 to 0.5, P=0.24).

The multiple linear regression analysis of the relation between the LVEF change and treatment, adjusted for age, T2DM, BMI, LVEF, ischaemic heart disease, and eGFR, did not change the overall conclusion.

There was no interaction with T2DM status for the LVEF change (P=0.59).

The atrial volume decreased significantly in the liraglutide group compared with the placebo group (mean difference −8.7 mL, 95% CI: −14.2 to −3.2, P=0.002).

At the end of the study, patients in the liraglutide group were able to walk 28±65 meters longer in the 6-minute walk test compared with 3±89 meters in the placebo group (mean difference 24 meters, 95% CI: 2-47, P=0.04).

Liraglutide treatment was associated with a weight loss of 2.2±3.1 kg. There was no change in the placebo group (0.0±3.0 kg).

Although systolic blood pressure (SBP) was reduced in the liraglutide group, there was no statistically significant difference between the treatment groups.

There was an increase in heart rate of on average 6±9 bpm in the liraglutide group and an average decrease of 1±8 bpm in the placebo group (mean difference 7 bpm, 95% CI: 5-9, P<0.0001).

After 24 weeks of treatment, HbA1c was reduced in the liraglutide group compared with the placebo group (mean difference −0.4%, 95% CI: −0.5 to −0.3, P<0.0001).

More patients experienced serious cardiac adverse events in the liraglutide group compared with the placebo group (10% vs. 3% resp., P=0.04). The events were one death caused by ventricular tachycardia (VT), non-fatal VT, atrial fibrillation requiring intervention, worsening of ischaemic heart disease, and one case of worsening HF.

Conclusion

In patients with stable chronic HF and reduced LVEF and T2DM, no difference with regard to changes in LVEF or other systolic function measures were observed between the liraglutide and the placebo group. On the other hand, liraglutide was associated with an substantial increased heart rate and more serious adverse events compared with placebo.